• Title/Summary/Keyword: Blood cAMP

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Effects of KATP Channel Blocker, cAMP and cGMP on the Cardiovascular Response of Adenosine A1 Agonist in the Spinal Cord of the Rats

  • Shin In-Chul
    • Biomolecules & Therapeutics
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    • v.14 no.2
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    • pp.119-124
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    • 2006
  • This study was performed to investigate the influence of the spinal adenosine $A_1$ receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by cyclic AMP (cAMP), cyclic GMP (cGMP) or potassium channel. Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawley rats. I.t. injection of adenosine $A_1$ receptor agonist, $N^6$-cyclohexyladenosine (CHA; 1, 5 and 10 nmol) produced dose dependent decrease of BP and HR and it was attenuated by pretreatment of 50 nmol of 8-cyclopentyl-1,3-dimethylxanthine, a specific adenosine $A_1$ receptor antagonist. Pretreatment with a cAMP analogue, 8-bromo-cAMP, also attenuated the depressor and bradycardiac effects of CHA (10 nmol), but not with cGMP analogue, 8-bromo-cGMP. Pretreatment with a ATP-sensitive potassium channel blocker, glipizide (20 nmol) also attenuated the depressor and bradycardiac effects of CHA (10 nmol). These results suggest that adenosine $A_1$ receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that this depressor and bradycardiac actions are mediated by cAMP and potassium channel.

Inhibitory Mechanism of Propranolol on the Effects of VIP in Peripheral Blood T-lymphocytes of Rat (흰쥐 말초혈액 T-림프구에서 Vasoactive Intestinal Polypeptide의 효과에 대한 Propranolol의 억제 기전)

  • Ahn, Young-Soo;Choo, Sung-Yee;Kang, Dong-Won;Lee, Sang-Hun
    • The Korean Journal of Pharmacology
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    • v.31 no.2
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    • pp.219-231
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    • 1995
  • Vasoactive intestinal polypeptide(VIP) and ${\beta}-adrenergic$ agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a ${\beta}-adrenergic$ receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to ${\beta}-adrenergic$ receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.

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Correlative Effects of Yookmijihwangtang(六味地黃湯) on the T helper cell count, Blood cAMP, Testosterone and Cortisol (육미지황탕(六味地黃湯)이 생리활성지표(生理活性指標)와 임파구세포수(淋巴球細胞數)에 미치는 영향(影響))

  • Kim, Young-Kuen;Ryu, Bong-Ha;Park, Dong-Won;Ryu, Ki-Won
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.4 no.1
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    • pp.89-110
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    • 1998
  • Yookmijihwangtang has been widely used oriental herb prescriptions, which is healing some discuss that come from insufficiency of innate essence and deficiency of kidney Ki. The meaning of healing discusses tonification of insufficient innate essence and insufficient kidney Ki can be regarded as reinforcement of wholely power of keeping homeostasis, that is correlated with immuno-responsibility which protects subject from outer antigen to keep normal vital condition. This study was aimed to investigate correlative effects of Yookmijihwangtang water abstract on the RBC, WBC, blood CD4+ T helper cell count, blood testosterone, blood cAMP and blood cortisol. 40 Sprague-Dawley male rats were divided into 5 groups(Normal, Control, Sample I, Sample II, Sample III), 6 animals in every group. Normal group was not treated anything, control group was administrated normal saline in the same dosage of Sample I. 3 Sample groups were received some of Yookmijihwangtang water abstract at one time per 24 hours during 5 days in different dosage. Sample I(1/310pack/ml), Sample II(1/62pack/ml), Sample III(1/2.4pack/ml). After finishing treatment, all experimental subjects were killed for blood sample on RBC, WBC, blood CD4+ T helper cell count, spleen CD4+ T helper cell count, axillary lymph node CD4+ T helper cell count. blood cAMP, blood testosterone and blood cortisol. The results were as follows; RBC and WBC were increased in all sample groups. Blood CD4+ T helper cell count(CD4+ T cell count in the blood/whole lymphocyte count in the blood ${\times}100%$) was Normal $46.17{\pm}5.88$, Control $44.50{\pm}4.37$, Sample I $53.00{\pm}2.28$, Sample II $53.83{\pm}3.87$, Sample III $52.17{\pm}2.93$. By the 95% Duncan ANOVA all experimental groups(sample I, Sample II, Sample III) showed slight significant difference from Normal and Control. Blood cAMP(nmol/l) were Normal $1.12{\pm}0.17$, Control $1.16{\pm}0.32$, Sample I $0.46{\pm}0.07$, Sample II $0.44{\pm}0.04$, Sample III $0.54{\pm}0.04$. All experimental groups were singificantly different from both Normal and Control groups(p<0.05). Blood cortisol(nl/ml) were Normal $100.00{\pm}2.00$ Control $90.00{\pm}4.00$, Sample I $440.00{\pm}5.00$, Sample II $520.00{\pm}40.00$, Sample III $470.00{\pm}7.00$. Blood cortisol of all experimental groups were significantly increased(p<0.05). The results suggest that Yookmijihwangtang water abstract could be administrated to patients who have some diseases insufficient essence.

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Effects of Cyclic Nucleotides and Glipizide on the Cardiovascular Response of Baclofen in the Rats (흰쥐의 척수에서 Cyclic Nucleotides 및 Glipizide가 Baclofen의 심혈관반응에 미치는 영향)

  • Koh, Hyun-Chul;Ha, Ji-Hee;Shin, In-Chul
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.6
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    • pp.647-655
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    • 1997
  • The purpose of present study is to investigate the influence of a spinal gamma-aminobutyric acid B($GABA_B$) receptor on a central regulation of blood pressure(BP) and heart rate(HR), and to define its mechanism in the spinal cord. In urethane-anesthetized, d-tubocurarine-paralyzed and artificially ventilated male Sprague-Dawley rats, intrathecal administration of drugs were carried out using injection cannula(33-gauge stainless steel) through the guide cannula(PE 10) which was inserted intrathecally at lower thoracic level through the puncture of a atlantooccipital membrane. Intrathecal injection of an $GABA_B$ receptor agonist, baclofen(30, 60, 100 nmol) decreased both BP and HR dose-dependently. Pretreatment with 8-bromo-cAMP(50 nmol), a cAMP analog, or glipizide(50 nmol), a ATP-sensitive $K^+$ channel blocker, attenuated the depressor and bradycardic effects of baclofen(100 nmol), but not with 8-bromo-cGMP(50 nmol), a cGMP analog. These results suggest that the $GABA_B$ receptor in the spinal cord plays an inhibitory role in central cardiovascular regulation and that this depressor and bradycardic actions are mediated by the decrease of cAMP via the inhibition of adenylate cyclase and the opening of $K^+$ channel.

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Effects of L-arginine on Endothelium Derived Factors and Cyclic Nucleotides in Broilers under Low Ambient Temperature

  • Han, Bo;Yoon, Soonseek;Han, Hongryul;Wang, Xiaolong
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.11
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    • pp.1570-1574
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    • 2004
  • A flock of AA breed chickens were reared in peterstme brood-vait chamber and were provided with high energy pelleted feed. At 14 d of age, a total of 350 birds were randomly divided into 3 groups as follows: 100 birds were exposed to normal ambient temperature of 20$^{\circ}C$ for control group; 150 birds were exposed to lower ambient temperature of 11$^{\circ}C$ to induce ascites (treatment I); and another group of 100 birds were exposed to lower ambient temperature of 11$^{\circ}C$ and fed diet containing 1% L-arginine for ascitic prophylactic treatment (treatment II). Samples were collected from blood and abdominal fluid of chicken at 3, 4, 5, 6 and 7 wk of age subsequently, to analysis the contents of plasma endothelin (ET-1), angiotensin II (Ang II), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP). The results indicated that the contents of cAMP, cGMP, and Ang II in reatment I and ascitic broilers were higher than the corresponding control group (p<0.01, p<0.05), ET-1 of preascitic broilers were control group (p<0.05), while there was an insignificant difference with later ascitic broilers. The contents of cAMP and cGMP in treatment II were higher than the treatment I and control groups (p<0.01, p<0.05), whereas, the contents of Ang II were gradually decreased compared to the control group (p<0.05), the contents of ET-1 were insignificantly different. On further analysis, the increased plasma Ang II at low ambient temperature condition in broilers made endothelium cell secretion of increased ET-1, cAMP, cGMP and decreased NO. Therefore, low temperature accelerated ascites syndrome in broilers. Supplemently L-arginine can decrease ET-1, and increase cAMP and cGMP. It is concluded that cAMP mediated in broilers pulmonary hypertension syndrome.

Vanadate-Induced Renal cAMP and Malondialdehyde Accumulation Suppresses Alpha 1 Sodium Potassium Adenosine Triphosphatase Protein Levels

  • Eiam-Ong, Somchit;Nakchui, Yuyen;Chaipipat, Mookda;Eiam-Ong, Somchai
    • Toxicological Research
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    • v.34 no.2
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    • pp.143-150
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    • 2018
  • It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (${\alpha}_1$) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal ${\alpha}_1-Na$, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of ${\alpha}_1-Na$, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal ${\alpha}_1-Na$, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.

Effects of Selenium and Metallothionein on the Toxicity of Cadmium in Rats (카드뮴 투여후 셀레늄과 Metallothionein의 독성효과)

  • Ryu, Yong-Wun;Lee, Kee-Ho
    • Journal of Radiation Protection and Research
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    • v.17 no.1
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    • pp.11-19
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    • 1992
  • To find out an effective way of treating the toxicity of cadmium, concentrations of $K^+,\;Ca^{2+}$ and c-AMP, and activities of GOT and GPT in blood of rats were determined at definite time intervals after administration of cadmium to rats. Cadmium caused more decrease of $Ca^{2+}$ concentration than $K^+$ concentration but increases of GOT and GPT activities and of c-AMP concentrations. The decreased concentration of $Ca^{2+}$ was not recovered by selenium or metallothionein. However, the increased activities of GOT and GPT, and the c-AMP concentration were down regulated remarkably by selenium but not by metallothionein. These results suggested that selenium might have the compensate effects concerning toxic index against cadmium such as increases of GOT and GPT activities, and of c-AMP concentration.

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Spinach Saponin-Enriched Fraction Inhibits Platelet Aggregation in cAMP- and cGMP-Dependent Manner by Decreasing TXA2 Production and Blood Coagulation

  • Cho, Hyun-Jeong;Choi, Sun-A;Kim, Chun-Gyu;Jung, Tae-Sung;Hong, Jeong-Hwa;Rhee, Man-Hee;Park, Hye-Jin;Park, Hwa-Jin
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.218-223
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    • 2011
  • In this study, we investigated the effect of spinach saponin-enriched fraction (SSEF) on collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation. SSEF inhibited collagen-induced platelet aggregation, and which was involved in the inhibition of thromboxane $A_2$ ($TXA_2$) production, an intracellular $Ca^{2+}$-agonist as an aggregation-inducing autacoidal molecule. In addition, SSEF significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular $Ca^{2+}$-antagonists as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that SSEF might inhibit $Ca^{2+}$-elevation and $TXA_2$ formation by increasing the production of $Ca^{2+}$-antagonistic molecules cAMP and cGMP. These mean that SSEF is a potent inhibitor of collagen-stimulated platelet aggregation. On the other hand, prothrombin time (PT) and activated partial thromboplastin time (APTT) were potently prolonged by SSEF. These findings suggest that SSEF prolongs the internal time between the conversion of fibrinogen to fibrin. Accordingly, our data demonstrate that SSEF may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.

Anti-Thrombotic Effects of Egg Yolk Lipids In Vivo

  • Cho, Hyun-Jeong;Ju, Young-Cheol;Park, Hwa-Jin
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.377-380
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    • 2010
  • In this study, we investigated the effect of egg yolk lipids (EYL) on collagen ($10\;{\mu}g/ml$)-stimulated platelet aggregation in vivo. Dietary EYL significantly inhibited collagen-induced platelet aggregation, in addition, increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular $Ca^{2+}$-antagonist as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that EYL inhibits the collagen-induced platelet aggregation by up-regulating the cAMP and cGMP production. On the other hands, prothrombin time (PT) on extrinsic pathway of blood coagulation was potently prolonged by dietary EYL in vivo. These findings suggest that EYL prolongs the internal time between the conversion of fibrinogen to fibrin. Accordingly, our data demonstrate that EYL may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.

Community-acquired Extended-spectrum and Plasmid-mediated ampC Beta-lactamase-producing Multidrug-resistant Enterobacter cloacae Septicaemia in a Cat with Euthyroid Sick Syndrome (정상 갑상샘 질환 증후군 고양이의 지역사회획득 광범위 및 플라스미드 유래 ampC beta-lactamase 양성 다약제내성 Enterobacter cloacae 패혈증)

  • Han, Jae-Ik;Na, Ki-Jeong
    • Journal of Veterinary Clinics
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    • v.32 no.2
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    • pp.191-195
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    • 2015
  • A 7-year-old castrated male Korean Shorthair cat was referred with lethargy and anorexia. Laboratory examination revealed moderate degenerative changes of peripheral neutrophils on blood smear examination and decreased levels of free and total thyroxine ($T_4$) as well as bacterial growth on blood culture. Molecular analyses of the 16S ribosomal RNA gene and heat shock protein 60 gene confirmed the bacterium as Enterobacter cloacae. A minimal inhibitory concentration test showed multidrug resistance of the bacterium against 16 antibiotics. Polymerase chain reaction (PCR) and subsequent sequencing specifically for $bla_{TEM}$, $bla_{SHV}$, $bla_{CTX-M}$, and plasmid-mediated ampC genes revealed positive results to $bla_{TEM-1}$, $bla_{CTX-M-15}$, and plasmid-mediated $bla_{ACT-1}$ genes, indicating that the isolated bacterium contains plasmids containing genes encoding extended-spectrum beta-lactamase and plasmid-mediated ampC beta-lactamase. After 1 month of treatment with antibiotics and levothyroxine, the cat's condition improved; both the thyroid function test and the blood culture showed no abnormalities. This is the first report of community-acquired multidrug-resistant E. cloacae-induced euthyroid sick syndrome in a cat. By the prompt diagnostic procedures and properly selected antibiotic therapy, the cat was recovered from the multidrug-resistant bacterium-induced septicaemia.